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    Summary
    EudraCT Number:2020-001979-33
    Sponsor's Protocol Code Number:AL-TNBC-01
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:GB - no longer in EU/EEA
    Date on which this record was first entered in the EudraCT database:2020-10-09
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedUK - MHRA
    A.2EudraCT number2020-001979-33
    A.3Full title of the trial
    A Phase 2, Multicenter, Open-label, Single-arm Study of AL101 Monotherapy in Patients with Notch-activated Triple Negative Breast Cancer
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study of investigational medicinal product AL101 in adults with breast cancer
    A.3.2Name or abbreviated title of the trial where available
    TENACITY
    A.4.1Sponsor's protocol code numberAL-TNBC-01
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorAyala Pharmaceuticals, Inc.
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportAyala Pharmaceuticals, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAyala Pharmaceuticals, Inc.
    B.5.2Functional name of contact pointClinical Trial Information
    B.5.3 Address:
    B.5.3.1Street Addressc/o MWE Corporate Services, 1007 N. Orange st., 4th Floor
    B.5.3.2Town/ cityWilmington
    B.5.3.3Post codeDE 19801
    B.5.3.4CountryUnited States
    B.5.6E-mailclinicaltrials@ayalapharma.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.2Product code AL101
    D.3.4Pharmaceutical form Solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INN-
    D.3.9.1CAS number 1401066-79-2
    D.3.9.2Current sponsor codeAL101
    D.3.9.4EV Substance CodeSUB32063
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1.2
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Notch Activated Recurrent or Metastatic Triple Negative Breast Cancer
    E.1.1.1Medical condition in easily understood language
    Breast cancer
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10075566
    E.1.2Term Triple negative breast cancer
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To evaluate the efficacy of AL101 monotherapy in subjects with Notch-activated recurrent or metastatic TNBC
    E.2.2Secondary objectives of the trial
    - Efficacy - Secondary
    - To evaluate the safety and tolerability of AL101 monotherapy in subjects with recurrent or metastatic TNBC
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. At least 18 years of age (inclusive) at the time of signing the Informed Consent Form (ICF).
    2. Have at least one measurable lesion per RECIST v1.1.
    3. Have formalin-fixed paraffin-embedded (FFPE) tissue available from a metastatic lesion; a tumor block or 25 unstained slides from an archived (within 2 years) or fresh tumor samples (core or punch needle biopsy) are acceptable.
    4. Documented tumor progression following no more than 3 lines of systemic chemotherapy, PARP inhibitor therapy or immunotherapy for metastatic disease, as appropriate. Of note, neoadjuvant and adjuvant therapy will not count as prior lines of therapy.
    5. Histologically confirmed diagnosis of inoperable locally advanced or metastatic TNBC defined as ER and progesterone receptor staining <10%, and HER2-negative defined as IHC 0 to 1+. Note, if IHC is equivocal then do fluorescence in situ hybridization (FISH) or in situ hybridization (ISH); negative will be acceptable. Note: if FISH or ISH is equivocal then further assessment is allowed with Sponsor written approval.
    6. Documented Notch activation from tumor biopsy results from within the last 2 years from a commercially available NGS assay, LDT or other validated IUO clinical trial assay.
    7. Female or Male subjects.
    8. Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of IP and must agree to have a pregnancy test at least every cycle (4 weeks). An extension up to 72 hours is permissible in situations where results cannot be obtained within the standard 24-hour window. Contraception use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
    9. WOCBP must agree to use a highly effective birth control during the study (prior to the first dose with AL101 and for 120 days after the last dose), if conception is possible during this interval. Female subjects are considered to not be of childbearing potential if they have a history of hysterectomy or are post-menopausal defined as no menses for 12 months without an alternative medical cause.
    10. Male subjects with partners who are WOCBP should use a combination of the methods specified in Section 10.4 for the women along with a male condom during the study and for 120 days after the last dose of IP, unless permanently sterile by bilateral orchidectomy.
    11. Capable of giving signed informed consent form (ICF) which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
    E.4Principal exclusion criteria
    1. A known additional malignancy that is progressing or requires active treatment that is considered medically active and may interfere in the ability to detect responses in this subject. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that have undergone potentially curative therapy or in situ cervical cancer. Any exceptions should be discussed with the Sponsor’s Medical Monitor.
    2. BC that, in the opinion of the investigator, is considered amenable to potentially curative treatment.
    3. Symptomatic central nervous system (CNS) metastases. Subjects with asymptomatic CNS metastases as well as those with previously treated CNS metastases are eligible for enrollment in the study if at least 28 days has elapsed since definitive treatment (either surgery, whole brain radiotherapy, stereotactic radiation), steroid therapy is either not required or dose has been weaned off over last 14 days, and the subject is deemed
    clinically stable by the investigator.
    4. Current or recent (within 2 months of IP administration) gastrointestinal (GI) disease or disorders that increase the risk of diarrhea, such as inflammatory bowel disease and Crohn’s disease. Non-chronic conditions (e.g., infectious diarrhea) that are completely resolved for at least 2 weeks prior to starting IP are not exclusionary.
    5. Developed immune-mediated colitis with immunotherapy unless resolved to G1 or lower and without requirement of steroid treatment for at least 14 days prior to first dose of IP.
    6. Peripheral neuropathy ≥ Grade 2 for at least 14 days prior to first dose of IP.
    7. Evidence of uncontrolled, active infection, requiring systemic anti-bacterial, anti-viral or anti-fungal therapy ≤7 days prior to administration of IP such as known active infection with hepatitis B, hepatitis C, or human immunodeficiency virus (HIV).
    8. Unstable or severe uncontrolled medical condition (e.g., unstable cardiac or pulmonary function or uncontrolled diabetes) or any important medical illness or abnormal laboratory finding that would, in the investigator’s judgment, increase the risk to the subject associated with his or her participation in the study.
    9. Pregnant or breastfeeding or expecting to conceive children within the projected duration of the study.
    10. Eastern Cooperative Oncology Group (ECOG) performance status ≥2.
    11. Abnormal organ and marrow function defined as:
    a. neutrophils <1000/mm3,
    b. platelet count <75,000/mm3,
    c. hemoglobin <8 g/dL,
    d. total bilirubin >1.5 x upper limit of normal (ULN) (except known Gilbert’s syndrome whereby the total bilirubin must be < 5 mg/dL),
    e. aspartate aminotransferase (AST) and alanine aminotransferase (ALT) >2.5 x ULN OR >5 x ULN for subjects with liver metastases,
    f. serum creatinine > ULN and creatinine clearance (CrCl) <50 mL/min (calculation of CrCl will be based on acceptable institution standard),
    g. uncontrolled triglyceride ≥Grade 2 elevations per CTCAE v5.0 (>300 mg/dL or >3.42 mmol/L).
    12. Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
    13. Mean QT interval corrected for heart rate using Fridericia’s formula (QTcF) ≥480 msec.
    14. Completed palliative radiation therapy < 7 days prior to initiating IP.
    15. Prior treatment with gamma secretase inhibitors. Prior treatment with anti-Notch antibodies may be allowed upon discussion with the Sponsor’s medical monitor.
    16. Last chemotherapy, biologic, or investigational therapy agent at least 4 weeks or 5 halflives (whichever is shorter) prior to initiating IP; at least 6 weeks if the last regimen included BCNU or mitomycin C. Prior treatment with investigational monoclonal antibody will be reviewed case-by-case by the Sponsor.
    17. Receiving chronic systemic steroid therapy (in dosing exceeding 10 mg/day of prednisone or equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of IP. The use of physiologic doses of corticosteroids may be approved after consultation with the Sponsor.
    18. Use of strong inhibitors of CYP3A4 within 1 week or 5 half-lives (whichever is longer) or strong inducers of CYP3A4 within 2 weeks or 5 half-lives (whichever is longer).
    19. Concurrent enrolment in another clinical study, unless it is an observational (noninterventional) clinical study or during the follow-up period of an interventional study.
    20. Life expectancy of less than 3 months.
    21. Hypersensitivity to AL101 and any of its excipients.
    E.5 End points
    E.5.1Primary end point(s)
    Proportion of subjects who demonstrate an overall response rate (ORR), defined as partial response (PR) + complete response (CR) as assessed by investigator based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
    E.5.1.1Timepoint(s) of evaluation of this end point
    Throughout the course of the study
    E.5.2Secondary end point(s)
    - Clinical benefit response rate (CBR) defined as CR +PR + stable disease (SD) by investigator review based on RECIST v1.1.
    - Duration of response (DOR) by investigator review based on RECIST v1.1.
    - Progression free survival (PFS).
    - Proportion of subjects who have PFS at 6 months.
    - Overall survival (OS).
    - Quality of life (QoL) as determined by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30 questions (EORTC QLQ-C30) and Breast Cancer 45 questions (EORTC QLQ-BR45).
    - Frequency, duration and severity of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs).
    - Incidence of clinically significant abnormalities in laboratory parameters, electrocardiograms (ECGs), vital signs and physical examination.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Throughout the course of the study
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic Yes
    E.6.11Pharmacogenomic Yes
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised No
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other Yes
    E.8.1.7.1Other trial design description
    Simon two-stage optimal design
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial1
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned2
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA12
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Belgium
    France
    Israel
    Netherlands
    Spain
    United Kingdom
    United States
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    A subject is considered to have completed the study if he/she has completed EOS visit, 30 days after the last administration of the IMP.
    The end of the study is defined as the date of the last visit of the last subject in the study (LVLS).
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months0
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 58
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 15
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state6
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 30
    F.4.2.2In the whole clinical trial 73
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    No formal open-label is planned, subjects will go back to standard of care
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2020-12-16
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2020-12-16
    P. End of Trial
    P.End of Trial StatusGB - no longer in EU/EEA
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